This application addresses Broad Challenge Area (05) Comparative Effectiveness Research, and Specific Challenge Topic 05-AG-104: Planning Grants and Pilot Studies for Comparisons of Management Strategies for Older Patients with Multiple Coexisting Conditions. As the population of the United States ages, there is an increased risk of cognitive impairment and physical deconditioning. Physical exercise has been shown to have physical and health benefits in the elderly and there is increasing evidence that systematic exercise programs may enhance cognitive function. In addition, cognitive exercise programs developed by our group and others have shown to be promising in enhancing cognitive function in older adults with cognitive impairment. There is a paucity of data, however, on the following: a) The extent to which exercise can benefit older adults with mild cognitive impairment (MCI) b) The comparative effectiveness of exercise and cognitive training among persons with MCI c) The possible advantages of combined exercise and cognitive interventions for MCI The proposed investigation will offer the unique opportunity to investigate exercise- and cognitive-related training changes at cognitive and physiological levels. The study will assess the impact of exercise training, cognitive training, and a combination of exercise and cognitive training on physical fitness, inflammatory and immunological biomarkers, and cognitive function among Hispanic and non-Hispanic older adults with MCI. This represents the first study of its type to compare the efficacy of state of the art non-pharmacological interventions in MCI. The study has significant potential to improve cognitive and physical status as well as quality of life in older adults with MCI. With the aging of the population, there is an increasing need to develop interventions that can optimize and maintain cognitive and physical health. Mild Cognitive Impairment (MCI) is characterized by cognitive decline confirmed by objective cognitive testing that is greater than would be expected for an individual's age but insufficient to merit a diagnosis of dementia. Over 5 million older adults in the United States have MCI and it is increasingly recognized that this condition may adversely affect the ability to manage higher order activities of daily living and reduce quality of life. Individuals with MCI are also at a considerably higher risk for progression to dementia than their non-MCI peers. Any approach that could reduce the cognitive consequences of MCI in older adults would have considerable economic and social benefits to afflicted individuals, their families, and the country at large. The proposed study will examine the comparative effectiveness of a physical exercise intervention, a cognitive exercise intervention, and a combined physical plus cognitive intervention in older adults with MCI. This study is unique in that ) it would be the first to conduct a head-to-head comparison of a Physical Exercise Intervention, a Cognitive Exercise Intervention, a Combined Physical plus Cognitive Exercise Intervention, and a no-intervention control condition among older adults with MCI;2) a broad array of outcome variables will be examined including measures of cognitive functioning, physical endurance and fitness, biological activity (e.g., lipid profiles, immune and inflammatory response), and quality of life;3) the interventions will be administered to Hispanic and non-Hispanic older adults to ensure broad applicability to older adults with MCI in the US;4) the Combined PEI+CEI intervention will examine the possibility that the integration of the cognitive and the physical exercise intervention may result in greater effects than physical exercise or cognitive exercise alone. PUBLIC HEALTH RELEVANCE: The proposed investigation offers an empirical comparison of safe and non-invasive approaches that could improve the cognitive and physical health of older adults with MCI as well as their quality of life.